Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure.

The kidney and brain play critical roles in the regulation of blood pressure. Neuropeptide FF (NPFF), originally isolated from the bovine brain, has been suggested to contribute to the pathogenesis of hypertension. However, the roles of NPFF and its receptors, NPFF-R1 and NPFF-R2, in the regulation of blood pressure, via the kidney, are not known.

Transcriptional Regulatory Role of NELL2 in Preproenkephalin Gene Expression.

Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-likelike 2 (NELL2) on PPE gene expression.

Transcription Factor TonEBP Stimulates Hyperosmolality-Dependent Arginine Vasopressin Gene Expression in the Mouse Hypothalamus.

The hypothalamic neuroendocrine system is strongly implicated in body energy homeostasis. In particular, the degree of production and release of arginine vasopressin (AVP) in the hypothalamus is affected by plasma osmolality, and that hypothalamic AVP is responsible for thirst and osmolality-dependent water and metabolic balance. However, the osmolality-responsive intracellular mechanism within AVP cells that regulates AVP synthesis is not clearly understood.

A Role of Central NELL2 in the Regulation of Feeding Behavior in Rats.

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. hybridization and an im-munohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus.

Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice.

Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we report that hypothalamic PREP is predominantly expressed in the ventromedial nucleus (VMH), where it regulates glucose-induced neuronal activation. PREP knockdown mice (Prep(gt/gt)) exhibited glucose intolerance, decreased fasting insulin, increased fasting glucagon levels, and reduced glucose-induced insulin secretion compared with wild-type controls.

Participation of the central melanocortin system in metabolic regulation and energy homeostasis.

Obesity and metabolic disorders, such as type 2 diabetes and hypertension, have attracted considerable attention as life-threatening diseases not only in developed countries but also worldwide. Additionally, the rate of obesity in young people all over the world is rapidly increasing. Accumulated evidence suggests that the central nervous system may participate in the development of and/or protection from obesity.

Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding.

We found that leptin receptors were expressed in hypothalamic astrocytes and that their conditional deletion led to altered glial morphology and synaptic inputs onto hypothalamic neurons involved in feeding control. Leptin-regulated feeding was diminished, whereas feeding after fasting or ghrelin administration was elevated in mice with astrocyte-specific leptin receptor deficiency. These data reveal an active role of glial cells in hypothalamic synaptic remodeling and control of feeding by leptin.

Prolyl carboxypeptidase mRNA expression in the mouse brain.

Prolyl carboxypeptidase (PRCP), a serine protease, is widely expressed in the body including liver, lung, kidney and brain, with a variety of known substrates such as plasma prekallikrein, bradykinin, angiotensins II and III, and α-MSH, suggesting its role in the processing of tissue-specific substrates. In the brain, PRCP has been shown to inactivate hypothalamic α-MSH, thus modulating melanocortin signaling in the control of energy metabolism. While its expression pattern has been reported in the hypothalamus, little is known on the distribution of PRCP throughout the mouse brain.

Mechanistic basis and functional roles of long-term plasticity in auditory neurons induced by a brain-generated estrogen.

The classic estrogen 17β-estradiol (E2) was recently identified as a novel modulator of hearing function. It is produced rapidly, in an experience-dependent fashion, by auditory cortical neurons of both males and females. This brain-generated E2 enhances the efficiency of auditory coding and improves the neural and behavioral discrimination of auditory cues.

Fatty acid amide hydrolase ablation promotes ectopic lipid storage and insulin resistance due to centrally mediated hypothyroidism.

Fatty acid amide hydrolase (FAAH) knockout mice are prone to excess energy storage and adiposity, whereas mutations in FAAH are associated with obesity in humans. However, the molecular mechanism by which FAAH affects energy expenditure (EE) remains unknown. Here we show that reduced energy expenditure in FAAH(-/-) mice could be attributed to decreased circulating triiodothyronine and thyroxine concentrations secondary to reduced mRNA expression of both pituitary thyroid-stimulating hormone and hypothalamic thyrotropin-releasing hormone.

Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory.

Prolyl endopeptidase (PREP) is a phylogenetically conserved serine protease and, in humans and rodents, is highly expressed in the brain. Several neuropeptides associated with learning and memory and neurodegenerative disorders have been proposed to be the substrates for PREP, suggesting a possible role for PREP in these processes. However, its physiological function remains elusive.

Deletion of prolyl carboxypeptidase attenuates the metabolic effects of diet-induced obesity.

α-Melanocyte-stimulating hormone (α-MSH) is a critical regulator of energy metabolism. Prolyl carboxypeptidase (PRCP) is an enzyme responsible for its degradation and inactivation. PRCP-null mice (PRCP(gt/gt)) showed elevated levels of brain α-MSH, reduced food intake, and a leaner phenotype compared with wild-type controls.

Prolyl carboxypeptidase regulates energy expenditure and the thyroid axis.

Hypothalamic α-melanocyte-stimulating hormone (α-MSH) plays a central role in regulating energy uptake and expenditure. Prolyl carboxypeptidase (PRCP), a protease expressed in the hypothalamus, is responsible for the degradation of α-MSH. PRCP null animals (PRCP(gt/gt) mice) display elevated α-MSH in the hypothalamus, lower body weight, and are protected from diet induced obesity.

Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity.

Previous studies have proposed roles for hypothalamic reactive oxygen species (ROS) in the modulation of circuit activity of the melanocortin system. Here we show that suppression of ROS diminishes pro-opiomelanocortin (POMC) cell activation and promotes the activity of neuropeptide Y (NPY)- and agouti-related peptide (AgRP)-co-producing (NPY/AgRP) neurons and feeding, whereas ROS-activates POMC neurons and reduces feeding. The levels of ROS in POMC neurons were positively correlated with those of leptin in lean and ob/ob mice, a relationship that was diminished in diet-induced obese (DIO) mice.

Neurochemical organization and experience-dependent activation of estrogen-associated circuits in the songbird auditory forebrain.

The classic steroid hormone estradiol is rapidly produced by central auditory neurons in the songbird brain and instantaneously modulates auditory coding to enhance the neural and behavioral discrimination of acoustic signals. Although recent advances highlight novel roles for estradiol in the regulation of central auditory processing, current knowledge on the functional and neurochemical organization of estrogen-associated circuits, as well as the impact of sensory experience in these auditory forebrain networks, remains very limited. Here we show that both estrogen-producing and -sensitive neurons are highly expressed in the caudomedial nidopallium (NCM), the zebra finch analog of the mammalian auditory association cortex, but not other auditory forebrain areas.

Regulation of the female rat estrous cycle by a neural cell-specific epidermal growth factor-like repeat domain containing protein, NELL2.

NELL2, a protein containing epidermal growth factor-like repeat domains, is predominantly expressed in the nervous system. In the mammalian brain, NELL2 expression is mostly neuronal. Previously we found that NELL2 is involved in the onset of female puberty by regulating the release of gonadotropin-releasing hormone (GnRH), and in normal male sexual behavior by controlling the development of the sexually dimorphic nucleus of the preoptic area (POA).

Expression and rapid experience-dependent regulation of type-A GABAergic receptors in the songbird auditory forebrain.

GABAergic transmission influences sensory processing and experience-dependent plasticity in the adult brain. Little is known about the functional organization of inhibitory circuits in the auditory forebrain of songbirds, a robust model extensively used in the study of central auditory processing of behaviorally relevant communication signals. In particular, no information is currently available on the expression and organization of GABAA receptor-expressing neurons.

Organization and development of zebra finch HVC and paraHVC based on expression of zRalDH, an enzyme associated with retinoic acid production.

The zRalDH gene encodes an aldehyde dehydrogenase associated with the conversion of retinaldehyde (the main vitamin A metabolite) into retinoic acid and its expression is highly enriched in the song control system of adult zebra finches (Taeniopygia guttata). Within song control nucleus HVC, zRalDH is specifically expressed in the neurons that project to area X of the striatum. It is also expressed in paraHVC, commonly considered a medial extension of HVC that is closely associated with auditory areas in the caudomedial telencephalon.